page_title: Duloxetine
section_title: History
hierarchical_section_title: Duloxetine / History
caption_attribution_description: Cymbalta 60mg
context_page_description: Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, and neuropathic pain. It is taken by mouth.
  Common side effects include dry mouth, nausea, feeling tired, dizziness, agitation, sexual problems, and increased sweating. Severe side effects include an increased risk of suicide, serotonin syndrome, mania, and liver problems. Antidepressant withdrawal syndrome may occur if stopped. There are concerns that use during the later part of pregnancy can harm the baby. It is a serotonin–norepinephrine reuptake inhibitor. How it works is not entirely clear.
  Duloxetine was approved for medical use in the United States in 2004. It is available as a generic medication. In 2017, it was the 46th most commonly prescribed medication in the United States, with more than 16 million prescriptions.
context_section_description: Duloxetine was created by Eli Lilly and Company researchers.  David Robertson; David Wong, a co-discoverer of fluoxetine; and Joseph Krushinski are listed as inventors on the patent application filed in 1986 and granted in 1990.  The first publication on the discovery of the racemic form of duloxetine known as LY227942, was made in 1988. The (+)-enantiomer, assigned LY248686, was chosen for further studies, because it inhibited serotonin reuptake in rat synaptosomes to twice the degree of the (–)-enantiomer. This molecule was subsequently named duloxetine.
  In 2001, Lilly filed a New Drug Application (NDA) for duloxetine with the US Food and Drug Administration. In 2003, however, the FDA "recommended this application as not approvable from the manufacturing and control standpoint" because of "significant cGMP (current Good Manufacturing Practice) violations at the finished product manufacturing facility" of Eli Lilly in Indianapolis. Additionally, "potential liver toxicity" and QTc interval prolongation appeared as a concern. The FDA experts concluded that "duloxetine can cause hepatotoxicity in the form of transaminase elevations. It may also be a factor in causing more severe liver injury, but there are no cases in the NDA database that clearly demonstrate this. Use of duloxetine in the presence of ethanol may potentiate the deleterious effect of ethanol on the liver." The FDA also recommended "routine blood pressure monitoring" at the new highest recommended dose of 120 mg, "where 24% patients had one or more blood pressure readings of 140/90 vs. 9% of placebo patients."
  After the manufacturing issues were resolved, the liver toxicity warning included in the prescribing information, and the follow-up studies showed that duloxetine does not cause QTc interval prolongation, duloxetine was approved by the FDA for depression and diabetic neuropathy in 2004. In 2007, Health Canada approved duloxetine for the treatment of depression and diabetic peripheral neuropathic pain.
  Duloxetine was approved for use of stress urinary incontinence (SUI) in the EU in 2004. In 2005, Lilly withdrew the duloxetine application for stress urinary incontinence (SUI) in the U.S., stating that discussions with the FDA indicated "the agency is not prepared at this time to grant approval ... based on the data package submitted." A year later Lilly abandoned the pursuit of this indication in the U.S. market.
  The FDA approved duloxetine for the treatment of generalized anxiety disorder in February 2007.
  Cymbalta generated sales of nearly $5 billion in 2012 with $4 billion of that in the U.S., but its patent protection terminated January 1, 2014. Lilly received a six-month extension beyond June 30, 2013 after testing for the treatment of depression in adolescents, which may produce $1.5 billion in added sales.  It was the most prescribed antidepressant in 2013–14.
  The first generic duloxetine was marketed by Dr. Reddy.
caption: Cymbalta (duloxetine) 60mg
exif: {}